Gardner's syndrome is an hereditary defect (an autosomal dominant) resulting in tumors of skin, mesentery and bone as well as colonic polyps and cancer. Initial observations on cultured skin fibroblasts from such patients have indicated that simian virus 40 transforms them at a frequency ten-fold higher than normal. This in vitro expression of the Gardner's trait at the cellular level provides an experimental model for human carcinogenesis. We will attempt to determine what it is that these cells contribute which so enhances the establishment of transformation. The stages of SV40 transformation as now understood are characterized by a series of molecular events which we will measure. We will measure: appearance of uncoated virus in the nucleus; transcription of viral DNA; induction of T-antigen; integration of viral DNA into the host genome; viral induction of DNA replication; changes in growth properties; and release of infective virus. The relative simplicity of SV40 and of Gardner's syndrome's transmission and expression encourages our hope of characterizing their interaction at the molecular level.